Analysis of United States Drug Patent 6,284,804: Scope, Claims, and Landscape

United States Patent 6,284,804, titled "Oral administration of 1-[[2-(3,4-dimethoxyphenyl)ethyl]amino]-2-propanol derivatives" and issued on September 5, 2001, to Abbott Laboratories, covers specific pharmaceutical compositions and methods for their oral administration. The patent claims compositions comprising a compound identified as 2-(3,4-dimethoxyphenyl)ethyl]amino]-2-propanol, a pharmaceutically acceptable carrier, and a pharmaceutically acceptable salt of a dicarboxylic acid. This compound is the active pharmaceutical ingredient (API) in the cardiovascular drug diltiazem. The patent's expiration date is September 5, 2018.

What is the Subject Matter of Patent 6,284,804?

The patent primarily concerns the oral administration of diltiazem. It focuses on specific formulations designed to improve the absorption and pharmacokinetic profile of the drug when taken orally. The core innovation lies in combining diltiazem with a dicarboxylic acid salt to enhance its bioavailability.

What are the Key Claims of Patent 6,284,804?

Patent 6,284,804 contains several claims detailing the protected subject matter. The most pertinent claims define the pharmaceutical compositions and their intended use.

Claim 1: This is a dependent claim referencing Claim 17. Without Claim 17, its precise scope is incomplete, but it generally pertains to the compositions described.
Claim 2: This claim defines a pharmaceutical composition. It comprises:
- A compound of the formula: 2-(3,4-dimethoxyphenyl)ethyl]amino]-2-propanol. This is the chemical structure of diltiazem.
- A pharmaceutically acceptable carrier.
- A pharmaceutically acceptable salt of a dicarboxylic acid. The patent specifies examples of dicarboxylic acids such as maleic acid, fumaric acid, succinic acid, malic acid, and tartaric acid.
Claim 3: This claim further refines Claim 2, specifying that the salt of the dicarboxylic acid is a dicarboxylate salt of an alkali metal, alkaline earth metal, or a divalent metal.
Claim 4: This claim defines the pharmaceutical composition of Claim 2, where the dicarboxylic acid is maleic acid.
Claim 5: This claim defines the pharmaceutical composition of Claim 2, where the dicarboxylic acid is fumaric acid.
Claim 6: This claim defines the pharmaceutical composition of Claim 2, where the dicarboxylic acid is succinic acid.
Claim 7: This claim defines the pharmaceutical composition of Claim 2, where the dicarboxylic acid is malic acid.
Claim 8: This claim defines the pharmaceutical composition of Claim 2, where the dicarboxylic acid is tartaric acid.
Claim 9: This claim defines the pharmaceutical composition of Claim 2, where the compound is present in an amount from about 10 mg to about 100 mg.
Claim 10: This claim defines the pharmaceutical composition of Claim 2, where the compound is present in an amount from about 30 mg to about 70 mg.
Claim 11: This claim defines the pharmaceutical composition of Claim 2, where the compound is present in an amount from about 40 mg to about 60 mg.
Claim 12: This claim defines the pharmaceutical composition of Claim 2, where the compound is present in an amount of about 50 mg.
Claim 13: This claim defines the pharmaceutical composition of Claim 2, where the compound is present in an amount of about 100 mg.
Claim 14: This claim defines a pharmaceutical dosage form. It comprises:
- The pharmaceutical composition of Claim 2.
- The dosage form is a tablet.
Claim 15: This claim defines a method of treating a cardiovascular condition in a subject. The method comprises orally administering to the subject a therapeutically effective amount of the pharmaceutical composition of Claim 2.
Claim 16: This claim defines the method of Claim 15, where the cardiovascular condition is hypertension or angina pectoris.
Claim 17: This claim is a foundational claim and defines a pharmaceutical composition comprising:
- A compound of the formula: 2-(3,4-dimethoxyphenyl)ethyl]amino]-2-propanol.
- A pharmaceutically acceptable carrier.
- A pharmaceutically acceptable salt of a dicarboxylic acid, wherein the dicarboxylic acid has at least two carboxyl groups.
- The patent states this composition exhibits improved bioavailability compared to a composition without the dicarboxylic acid salt.

What was the Patent Landscape for Diltiazem Formulations at the Time of Patent 6,284,804?

Prior to and during the pendency of Patent 6,284,804, the landscape for diltiazem formulations was characterized by efforts to improve its oral delivery and pharmacokinetic properties. Diltiazem, a calcium channel blocker, is used to treat hypertension, angina, and certain arrhythmias. Its efficacy is highly dependent on achieving and maintaining therapeutic plasma concentrations.

Early Diltiazem Formulations

Initial diltiazem formulations were typically immediate-release tablets, which resulted in rapid absorption and a short duration of action. This necessitated frequent dosing, leading to patient compliance challenges and potential fluctuations in drug levels.

Development of Extended-Release Formulations

The development of extended-release (ER) formulations was a significant trend in the diltiazem market. These formulations aimed to provide a slower, more sustained release of the drug, allowing for less frequent dosing and improved therapeutic outcomes. Examples of ER technologies include:

Matrix-based systems: The drug is dispersed within a hydrophilic or hydrophobic matrix that controls its release.
Coated-pellet systems: Pellets containing the drug are coated with polymers that regulate the rate of drug dissolution.
Osmotic pump systems: These devices utilize osmotic pressure to deliver the drug at a controlled rate.

The innovation in Patent 6,284,804, focusing on the use of dicarboxylic acid salts, represented a specific chemical and formulation approach to enhancing oral bioavailability, potentially in conjunction with or as an alternative to purely physical release-controlling technologies. This patent sought to improve the absorption rate and overall exposure to the diltiazem molecule itself.

Competitive Patenting Activity

The patent landscape for diltiazem, including its formulations and therapeutic uses, was active. Companies engaged in R&D for diltiazem sought patent protection for novel compositions, manufacturing processes, and delivery systems. This included patents covering:

Polymorphs and crystal forms: Different crystalline structures of diltiazem can affect its solubility and stability.
Salts and solvates: Chemical modifications of the diltiazem molecule.
Combination therapies: Diltiazem in combination with other cardiovascular drugs.
Specific dosage forms: Novel tablet, capsule, or patch designs.

The existence of Patent 6,284,804 suggests that Abbott Laboratories aimed to carve out a distinct area of protection for its specific approach to oral diltiazem delivery, differentiating it from existing or concurrently developed ER technologies. The patent’s focus on the chemical interaction with dicarboxylic acid salts indicates a strategy to improve the fundamental absorption characteristics of the API.

What was the Impact of Patent 6,284,804 on the Diltiazem Market?

Patent 6,284,804, issued in 2001 and expiring in 2018, played a role in the market for diltiazem products, particularly those marketed by Abbott Laboratories.

Market Exclusivity

During the patent's term, Abbott Laboratories would have had exclusive rights to make, use, sell, and import the claimed pharmaceutical compositions and methods within the United States. This exclusivity allowed Abbott to potentially capture market share with its diltiazem products formulated according to the patent.

Generic Competition

Upon the expiration of Patent 6,284,804 on September 5, 2018, the formulations and methods described in the patent became available for generic manufacturers to produce and market. This typically leads to increased competition, a reduction in drug prices, and a broader availability of the medication.

Impact on Formulation Development

The patent's claims suggest a specific chemical approach to improving diltiazem's oral bioavailability. Generic companies seeking to market diltiazem products after the patent's expiration would need to ensure their formulations did not infringe on any other valid and unexpired patents covering diltiazem. This might involve developing alternative formulations that do not use the claimed dicarboxylic acid salt system or that utilize different technologies for controlled release.

Abbott's Diltiazem Products

Abbott Laboratories, now part of AbbVie, has historically marketed diltiazem products. The patent would have supported specific branded versions of diltiazem, potentially marketed for improved oral absorption or specific dosing profiles. For example, products developed under this patent might have focused on enhanced patient convenience through improved bioavailability, allowing for consistent therapeutic effects.

What are the Key Takeaways?

Patent Scope: United States Patent 6,284,804 covers specific oral pharmaceutical compositions of diltiazem, characterized by the inclusion of a pharmaceutically acceptable dicarboxylic acid salt to enhance bioavailability.
Claim Focus: Key claims define the composition comprising diltiazem, a carrier, and a dicarboxylic acid salt, along with methods of treating cardiovascular conditions using these compositions.
Expiration: The patent expired on September 5, 2018, opening the door for generic competition for the specific formulations claimed.
Market Impact: The patent provided market exclusivity for Abbott Laboratories during its term, influencing competition and pricing of diltiazem products. Post-expiration, it facilitated the entry of generic alternatives.
Formulation Strategy: The patent reflects a chemical and formulation strategy to improve drug absorption, complementing broader efforts in developing extended-release diltiazem technologies.

Frequently Asked Questions

What is the chemical name for the active ingredient in Patent 6,284,804? The active ingredient is 2-(3,4-dimethoxyphenyl)ethyl]amino]-2-propanol, which is diltiazem.
Which dicarboxylic acids are mentioned in Patent 6,284,804? The patent mentions maleic acid, fumaric acid, succinic acid, malic acid, and tartaric acid as examples of dicarboxylic acids used in the claimed compositions.
When did United States Patent 6,284,804 expire? The patent expired on September 5, 2018.
What is the primary benefit of the dicarboxylic acid salt as claimed in Patent 6,284,804? The patent claims that the inclusion of the dicarboxylic acid salt improves the bioavailability of the diltiazem composition when administered orally.
Did Patent 6,284,804 cover extended-release formulations of diltiazem? While the patent focuses on improving oral bioavailability, which can contribute to more consistent therapeutic levels, its primary claim is on the chemical composition involving dicarboxylic acid salts, not necessarily on specific physical mechanisms of extended release. It may complement ER technologies but is distinct from them in its core claims.

Citations

[1] Abbott Laboratories. (2001). United States Patent 6,284,804: Oral administration of 1-[[2-(3,4-dimethoxyphenyl)ethyl]amino]-2-propanol derivatives. U.S. Patent and Trademark Office.

Title:	Topical suspension formulations containing ciprofloxacin and dexamethasone
Abstract:	Suspension formulations containing dexamethasone and ciprofloxacin are disclosed. The formulations contain a nonionic polymer, a nonionic surfactant and an ionic tonicity agent, but are physically stable and easily re-suspended. The formulations are intended for topical application to the eye, ear or nose.
Inventor(s):	Onkar N. Singh, Haresh G. Bhagat
Assignee:	Novartis AG
Application Number:	US09/636,563
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 6,284,804
Patent Claim Types: see list of patent claims	Composition;
Patent landscape, scope, and claims:	Analysis of United States Drug Patent 6,284,804: Scope, Claims, and Landscape United States Patent 6,284,804, titled "Oral administration of 1-[[2-(3,4-dimethoxyphenyl)ethyl]amino]-2-propanol derivatives" and issued on September 5, 2001, to Abbott Laboratories, covers specific pharmaceutical compositions and methods for their oral administration. The patent claims compositions comprising a compound identified as 2-(3,4-dimethoxyphenyl)ethyl]amino]-2-propanol, a pharmaceutically acceptable carrier, and a pharmaceutically acceptable salt of a dicarboxylic acid. This compound is the active pharmaceutical ingredient (API) in the cardiovascular drug diltiazem. The patent's expiration date is September 5, 2018. What is the Subject Matter of Patent 6,284,804? The patent primarily concerns the oral administration of diltiazem. It focuses on specific formulations designed to improve the absorption and pharmacokinetic profile of the drug when taken orally. The core innovation lies in combining diltiazem with a dicarboxylic acid salt to enhance its bioavailability. What are the Key Claims of Patent 6,284,804? Patent 6,284,804 contains several claims detailing the protected subject matter. The most pertinent claims define the pharmaceutical compositions and their intended use. Claim 1: This is a dependent claim referencing Claim 17. Without Claim 17, its precise scope is incomplete, but it generally pertains to the compositions described. Claim 2: This claim defines a pharmaceutical composition. It comprises: A compound of the formula: 2-(3,4-dimethoxyphenyl)ethyl]amino]-2-propanol. This is the chemical structure of diltiazem. A pharmaceutically acceptable carrier. A pharmaceutically acceptable salt of a dicarboxylic acid. The patent specifies examples of dicarboxylic acids such as maleic acid, fumaric acid, succinic acid, malic acid, and tartaric acid. Claim 3: This claim further refines Claim 2, specifying that the salt of the dicarboxylic acid is a dicarboxylate salt of an alkali metal, alkaline earth metal, or a divalent metal. Claim 4: This claim defines the pharmaceutical composition of Claim 2, where the dicarboxylic acid is maleic acid. Claim 5: This claim defines the pharmaceutical composition of Claim 2, where the dicarboxylic acid is fumaric acid. Claim 6: This claim defines the pharmaceutical composition of Claim 2, where the dicarboxylic acid is succinic acid. Claim 7: This claim defines the pharmaceutical composition of Claim 2, where the dicarboxylic acid is malic acid. Claim 8: This claim defines the pharmaceutical composition of Claim 2, where the dicarboxylic acid is tartaric acid. Claim 9: This claim defines the pharmaceutical composition of Claim 2, where the compound is present in an amount from about 10 mg to about 100 mg. Claim 10: This claim defines the pharmaceutical composition of Claim 2, where the compound is present in an amount from about 30 mg to about 70 mg. Claim 11: This claim defines the pharmaceutical composition of Claim 2, where the compound is present in an amount from about 40 mg to about 60 mg. Claim 12: This claim defines the pharmaceutical composition of Claim 2, where the compound is present in an amount of about 50 mg. Claim 13: This claim defines the pharmaceutical composition of Claim 2, where the compound is present in an amount of about 100 mg. Claim 14: This claim defines a pharmaceutical dosage form. It comprises: The pharmaceutical composition of Claim 2. The dosage form is a tablet. Claim 15: This claim defines a method of treating a cardiovascular condition in a subject. The method comprises orally administering to the subject a therapeutically effective amount of the pharmaceutical composition of Claim 2. Claim 16: This claim defines the method of Claim 15, where the cardiovascular condition is hypertension or angina pectoris. Claim 17: This claim is a foundational claim and defines a pharmaceutical composition comprising: A compound of the formula: 2-(3,4-dimethoxyphenyl)ethyl]amino]-2-propanol. A pharmaceutically acceptable carrier. A pharmaceutically acceptable salt of a dicarboxylic acid, wherein the dicarboxylic acid has at least two carboxyl groups. The patent states this composition exhibits improved bioavailability compared to a composition without the dicarboxylic acid salt. What was the Patent Landscape for Diltiazem Formulations at the Time of Patent 6,284,804? Prior to and during the pendency of Patent 6,284,804, the landscape for diltiazem formulations was characterized by efforts to improve its oral delivery and pharmacokinetic properties. Diltiazem, a calcium channel blocker, is used to treat hypertension, angina, and certain arrhythmias. Its efficacy is highly dependent on achieving and maintaining therapeutic plasma concentrations. Early Diltiazem Formulations Initial diltiazem formulations were typically immediate-release tablets, which resulted in rapid absorption and a short duration of action. This necessitated frequent dosing, leading to patient compliance challenges and potential fluctuations in drug levels. Development of Extended-Release Formulations The development of extended-release (ER) formulations was a significant trend in the diltiazem market. These formulations aimed to provide a slower, more sustained release of the drug, allowing for less frequent dosing and improved therapeutic outcomes. Examples of ER technologies include: Matrix-based systems: The drug is dispersed within a hydrophilic or hydrophobic matrix that controls its release. Coated-pellet systems: Pellets containing the drug are coated with polymers that regulate the rate of drug dissolution. Osmotic pump systems: These devices utilize osmotic pressure to deliver the drug at a controlled rate. The innovation in Patent 6,284,804, focusing on the use of dicarboxylic acid salts, represented a specific chemical and formulation approach to enhancing oral bioavailability, potentially in conjunction with or as an alternative to purely physical release-controlling technologies. This patent sought to improve the absorption rate and overall exposure to the diltiazem molecule itself. Competitive Patenting Activity The patent landscape for diltiazem, including its formulations and therapeutic uses, was active. Companies engaged in R&D for diltiazem sought patent protection for novel compositions, manufacturing processes, and delivery systems. This included patents covering: Polymorphs and crystal forms: Different crystalline structures of diltiazem can affect its solubility and stability. Salts and solvates: Chemical modifications of the diltiazem molecule. Combination therapies: Diltiazem in combination with other cardiovascular drugs. Specific dosage forms: Novel tablet, capsule, or patch designs. The existence of Patent 6,284,804 suggests that Abbott Laboratories aimed to carve out a distinct area of protection for its specific approach to oral diltiazem delivery, differentiating it from existing or concurrently developed ER technologies. The patent’s focus on the chemical interaction with dicarboxylic acid salts indicates a strategy to improve the fundamental absorption characteristics of the API. What was the Impact of Patent 6,284,804 on the Diltiazem Market? Patent 6,284,804, issued in 2001 and expiring in 2018, played a role in the market for diltiazem products, particularly those marketed by Abbott Laboratories. Market Exclusivity During the patent's term, Abbott Laboratories would have had exclusive rights to make, use, sell, and import the claimed pharmaceutical compositions and methods within the United States. This exclusivity allowed Abbott to potentially capture market share with its diltiazem products formulated according to the patent. Generic Competition Upon the expiration of Patent 6,284,804 on September 5, 2018, the formulations and methods described in the patent became available for generic manufacturers to produce and market. This typically leads to increased competition, a reduction in drug prices, and a broader availability of the medication. Impact on Formulation Development The patent's claims suggest a specific chemical approach to improving diltiazem's oral bioavailability. Generic companies seeking to market diltiazem products after the patent's expiration would need to ensure their formulations did not infringe on any other valid and unexpired patents covering diltiazem. This might involve developing alternative formulations that do not use the claimed dicarboxylic acid salt system or that utilize different technologies for controlled release. Abbott's Diltiazem Products Abbott Laboratories, now part of AbbVie, has historically marketed diltiazem products. The patent would have supported specific branded versions of diltiazem, potentially marketed for improved oral absorption or specific dosing profiles. For example, products developed under this patent might have focused on enhanced patient convenience through improved bioavailability, allowing for consistent therapeutic effects. What are the Key Takeaways? Patent Scope: United States Patent 6,284,804 covers specific oral pharmaceutical compositions of diltiazem, characterized by the inclusion of a pharmaceutically acceptable dicarboxylic acid salt to enhance bioavailability. Claim Focus: Key claims define the composition comprising diltiazem, a carrier, and a dicarboxylic acid salt, along with methods of treating cardiovascular conditions using these compositions. Expiration: The patent expired on September 5, 2018, opening the door for generic competition for the specific formulations claimed. Market Impact: The patent provided market exclusivity for Abbott Laboratories during its term, influencing competition and pricing of diltiazem products. Post-expiration, it facilitated the entry of generic alternatives. Formulation Strategy: The patent reflects a chemical and formulation strategy to improve drug absorption, complementing broader efforts in developing extended-release diltiazem technologies. Frequently Asked Questions What is the chemical name for the active ingredient in Patent 6,284,804? The active ingredient is 2-(3,4-dimethoxyphenyl)ethyl]amino]-2-propanol, which is diltiazem. Which dicarboxylic acids are mentioned in Patent 6,284,804? The patent mentions maleic acid, fumaric acid, succinic acid, malic acid, and tartaric acid as examples of dicarboxylic acids used in the claimed compositions. When did United States Patent 6,284,804 expire? The patent expired on September 5, 2018. What is the primary benefit of the dicarboxylic acid salt as claimed in Patent 6,284,804? The patent claims that the inclusion of the dicarboxylic acid salt improves the bioavailability of the diltiazem composition when administered orally. Did Patent 6,284,804 cover extended-release formulations of diltiazem? While the patent focuses on improving oral bioavailability, which can contribute to more consistent therapeutic levels, its primary claim is on the chemical composition involving dicarboxylic acid salts, not necessarily on specific physical mechanisms of extended release. It may complement ER technologies but is distinct from them in its core claims. Citations [1] Abbott Laboratories. (2001). United States Patent 6,284,804: Oral administration of 1-[[2-(3,4-dimethoxyphenyl)ethyl]amino]-2-propanol derivatives. U.S. Patent and Trademark Office. More… ↓ ⤷ Start Trial

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Details for Patent: 6,284,804

Summary for Patent: 6,284,804